Free zinc has been implicated in biological processes such as gene expression, apoptosis, enzyme regulation, and neurotransmission. Its role in such processes is unclear, largely due to the dearth of available real-time imaging techniques. Most zinc sensors rely on chelation enhanced fluorescence to image zinc. The goal of the project is to improve on these sensors in three areas. First, the current sensors often bind other transition metal ions more tightly than Zn(ll); one equivalent of these alternate metal ions effectively deactivates the current probes. Second, the fluorescence excitation and emission wavelengths need to be optimized. The emission wavelength, in particular, currently overlaps with many cellular chromophores. The project will seek to improve these properties by adding substituents to the fluorophore moiety of the sensor. Third, the zinc chemosensors often can only image part of the cell. The project will seek to incorporate protein-binding domains to target specific areas on the cell surface, specifically the ion channels that allow Zn(ll) influx into the post-synaptic neuron.